Balsalazide formulations and manufacture and use thereof
The invention relates to formulations and dosage schedules of balsalazide. The invention further relates to methods of producing pharmaceutical formulations of balsalazide.
1 . A pharmaceutical preparation to treat gastrointestinal disease comprising two daily doses of about 6 to about 6.6. grams per day of balsalazide or a pharmaceutically acceptable prodrug, salt, solvate, or clathrate thereof.
2 . (canceled)
3 . The pharmaceutical preparation of claim 1 , or wherein two daily doses comprise between about 3 to about 3.3 grams each.
4 . The pharmaceutical preparation of claim 1 , wherein the gastrointestinal disease is one or more of gastrointestinal bacterial infection or bacterial overgrowth, proctitis, or colon cancer.
5 - 12 . (canceled)
13 . The pharmaceutical preparation of claim 1 , further comprising a coating solution.
14 . (canceled)
15 . A package containing a pharmaceutical preparation to treat gastrointestinal disease comprising two daily doses of a balsalazide equivalent to about 6 to about 6.6 grams per day.
16 - 18 . (canceled)
19 . A method of treating gastrointestinal disease comprising administering to a subject in need thereof from between about 6 grams and about 6.7 grams per day of balsalazide in two daily doses.
20 - 26 . (canceled)
27 . A method of manufacturing a capsule, comprising:
granulating the balsalazide disodium and one or more excipients to form granules;
sizing the granules;
blending the granules for about 20 minutes to form a powder blend; and
encapsulating the powder blend.
28 . The method of claim 27 , wherein the one or more excipients comprise one or more of colloidal silicon dioxide or magnesium stearate.
29 . The method of claim 27 , wherein the excipients comprise from between about 2 to about 3% of the granules by weight.
30 . The method of claim 27 , wherein the sizing is with a 12 mesh screen.
31 . The method of claim 27 , wherein the blending is with a double cone blender.
32 . The method of claim 27 , further comprising polishing the encapsulated powder blend.
33 . The method of claim 27 , wherein from between about 700 mg and about 1200 mg of powder blend is encapsulated.
34 . A method for dissolution testing of balsalazide capsules, comprising:
stirring a balsalazide capsule prepared according to claim 19 in dissolution medium;
filtering the solution to form a filtrate;
sampling the filtrate; and
diluting the filtrate.
35 . The method of claim 34 , wherein the dissolution medium comprises 50 mM phosphate buffer of about pH 6.8; or wherein the diluting the filtrate comprises diluting 2 mL in about 98 mL of dissolution medium.
36 . (canceled)
37 . The method of claim 34 , further comprising analyzing the diluted filtrate.
38 . (canceled)
39 . A pharmaceutical preparation of balsalazide made by the process, comprising:
granulating a balsalazide disodium feed powder and one or more excipients to form granules;
blending the granules for about 20 minutes to form a powder blend; and encapsulating the powder blend,
wherein the two daily doses of about 6 grams per day of balsalazide or a pharmaceutically acceptable prodrug, salt, solvate, or clathrate thereof are administered.
40 . The pharmaceutical preparation of claim 39 , wherein the method further comprises sizing the granules before blending.
41 . The method of claim 39 , wherein the feed powder has an average particle diameter of from between about 8 to about 30 μm; or wherein the powder blend has an average particle diameter of from about 300 to about 675 μm; or wherein the powder blend has an specific surface area of from between about 3500 to about 8500 cm 2 /ml; or wherein the powder blend has a hardness (retention) of from between about 85 to about 90 (60 Mesh); or wherein the powder blend has a Loose Bulk Density (LBD) of from between about 0.67 to about 0.69 g/cc; or wherein the balsalazide disodium feed powder has a compression 20 K of from between about 1.28 to about 1.47 g/cc; or wherein the balsalazide disodium feed powder has a Tapped Bulk Density (TBD) of from between about 0.57 to about 0.63 g/cc; or wherein the balsalazide disodium feed powder has a moisture of from between about 0.10% and about 0.15%.
42 - 48 . (canceled)
49 . A pharmaceutical preparation of balsalazide made by the process, comprising:
granulating the balsalazide disodium and one or more excipients to form granules;
blending the granules for about 20 minutes to form a powder blend; and encapsulating the powder blend,
wherein the powder blend has an average particle diameter of from between about 300 to about 675 μm.
50 . The pharmaceutical preparation of claim 49 , wherein the method further comprises sizing the granules before blending.
51 . The pharmaceutical preparation of claim 49 , wherein the method further comprises sizing the granules before blending.
52 . The method of claim 49 , wherein the feed powder has an average particle diameter of from between about 8 to about 30 μm; or wherein the powder blend has an specific surface area of from between about 3500 to about 8500 cm 2 /ml; or wherein the powder blend has a hardness (retention) of from between about 85 to about 90 (60 Mesh); or wherein the powder blend has a Loose Bulk Density (LBD) of from between about 0.67 to about 0.69 g/cc; or, wherein the balsalazide disodium feed powder has a compression 20 K of from between about 1.28 to about 1.47 g/cc; or wherein the balsalazide disodium feed powder has a Tapped Bulk Density (TBD) of from between about 0.57 to about 0.63 g/cc or The method of claim 49 , wherein the balsalazide disodium feed powder has a moisture of from between about 0.10% and about 0.15%.
53 - 58 . (canceled)